Human monocyte activation induced by an anti-CD14 monoclonal antibody

Schütt, Christine; Ringel, Bruno; Nausch, Monika; Bažil, V; Hořejšı́, Václav; Neels, Peter; Walzel, Hermann; Jonas, Ludwig; Siegl, E; Friemel, H; Plantikow, A.

doi:10.1016/0165-2478(88)90162-9

Cited by 56 publications

(35 citation statements)

References 16 publications

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“…These findings are consistent with observations of Schutt et al (25), who demonstrated interleukin 1 secretion in response to anti-CD14 antibodies, but differ from our previous findings that incubation of whole blood with anti-CD14 antibodies caused no activation ofTNF-a secretion by monocytes (14). Preliminary data (unpublished) suggest that the ability of an anti-CD14 antibody to either activate a cell or to block activation depends on its ability to crosslink CD14.…”

supporting

confidence: 78%

“…This suggests that certain anti-CD14 antibodies, as described (25), may activate the CD14 receptor and that activation of NF-KB is among the early events triggered by ligation of CD14. We suggest that these data support a model in which LPS and the monoclonal IgG 3C10 may bind to different but overlapping epitopes on the CD14 molecule.…”

mentioning

confidence: 99%

“…After binding of the LPS-LBP complex to CD14 on the surface of monocytes, the monocyte is activated and produces TNF-a (14,25). CD14, which has been cloned and sequenced (26), is a glycoprotein with a phosphatidylinositol anchor and does not express a transmembrane or cytoplasmic domain (27).…”

mentioning

confidence: 99%

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CD14 is involved in control of human immunodeficiency virus type 1 expression in latently infected cells by lipopolysaccharide.

Bagasra

Wright

Seshamma

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Lipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1 (lIlV-1) long terminal repeat-directed transcription in transfected monocyte-macrophage cell lines and dramatically increases HIV-1 production in the latently infected monocyte-macrophage-like cell line U1. This response to LPS, however, can only be observed after pretreatment of the U1 cells with granulocytemacrophage colony-stimulating factor (GM-CSF). CD14, the differentiation antigen that acts as a receptor for complexes of LPS and LPS-binding protein, is now demonstrated to be involved in LPS-induced stimulation of HIV-1 replication.

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supporting

confidence: 78%

mentioning

confidence: 99%

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CD14 is involved in control of human immunodeficiency virus type 1 expression in latently infected cells by lipopolysaccharide.

Bagasra

Wright

Seshamma

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…La Jolla, CA). We used the following mouse monoclonal antibodies: MEM 18 (IgG I, which recognizes membrane CDI4 and both forms of sCDI4; gift of V. Bazil, Prague [3]); RoMo I (IgG2a; IBL, Hamburg, Germany) [18], 63D3 (lgG I), and 3C I0 (IgG2b; both purified by affinity chromatography from hybridoma culture supernatants; American Type Culture Collection, Rockville, MD); and My4 (IgG I) (Coulter, Luton, UK). rsCD 14 was immunopurified on immobilized 3C I0 from culture supernatants of CHO cells that were transfected with an expression vector containing truncated CDI4 cDNA (unpublished data).…”

Section: Methodsmentioning

confidence: 99%

Increased Circulating Soluble Cd14 Is Associated With High Mortality In Gram-Negative Septic Shock

Landmann

Zimmerli²,

Sansano³

et al. 1995

Journal of Infectious Diseases

193

124

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The soluble glycoprotein sCD 14 binds lipopolysaccharide, a complex that activates endothelial cells and that may be crucial in gram-negative sepsis, Therefore, serum sCD14 was analyzed in 54 patients with gram-negative septic shock and in 26 healthy controls, sCD14 was tested by ELISA and Western blotting, Patients had higher sCD14 concentrations than controls (median, 3.23 vs. 2.48 #!g/mL, P = .002). Increased levels were associated with high mortality (median, 4.2 #Lg/mL in nonsurvivors vs. 2.8 #!g/mL in survivors, P = .001). sCD14 was found in two isoforms (49 and 55 kDa) in monocyte cultures. In sera only one of either form was detectable. Controls had the 49-kDa form, and patients had either the 49-or 55-kDa form, but patients with high levels of sCD14 had only the 55-kDa form. Twenty-one (53%) of 39 with the 55-kDa form and 8 (57%) of 14 with the 49-kDa form died. Thus, the level of sCD14 but not its biochemical form had a prognostic value in patients with gram-negative septic shock.Lipopolysaccharide (LPS) plays a key role in the pathophysiology of sepsis [I]. The LPS receptor on myeloid cells is the phosphatidylinositol-Iinked membrane glycoprotein CD 14 [2]. CD 14 occurs in a membrane-associated form and as a soluble (s) molecule [3,4]. sCD 14 is derived from the monocytic cell line Mono-Mac 6 in two forms [5]: A 48-kDa form is shed from the membrane of monocytes and MonoMac 6 cells [6,7], and a 56-kDa form is detectable in metabolically labeled Mono-Mac 6 cells and in sCD 14 purified from urine [3,5]. The serum concentration of sCD 14 is ,...., I millionfold higher than that ofcytokines [8]. Although much is known about cytokine liberation during experimental endotoxemia or sepsis, little is known about sCD 14 in these conditions [9][10][11][12]. Because CD 14 is the principle LPS receptor, the serum concentration ofsCD 14 may be modified during endotoxemia or sepsis. The physiologic role of sCD 14 is unknown. It could act as a scavenger by neutralizing circulating LPS [13] shown that complexes ofsCD 14 with LPS activate these cells [14,15].We measured sequential serum concentrations of sCD 14 in 54 patients with gram-negative septic shock, compared these with levels in normal controls, and correlated sCD 14 levels with patient outcome. We also determined the biochemical form of serum sCD 14 by Western blotting and compared it with sCD 14 derived from normal monocytes. MethodsPatients. The study population comprised 54 patients (33 males, 21 females) with documented gram-negative septic shock. Their median age was 58 years (range, 7-78). All were part of a previously described study that compared the efficacy of J5 hyperimmunoglobulin (n = 22) with standard intravenously (iv) administered IgG (n = 32) (Sandoglobulin; Sandoz Pharmaceuticals, Basel, Switzerland) [16]. The etiology ofseptic shock was established by the isolation of gram-negative bacteria from blood in 37 patients (69%). Of these, 30 had monomicrobial and 7 had polymicrobial bacteremia. Seventeen patients (3 t %) had documented gram-nega...

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“…has been found to be elevated in sera from patients with sepsis or burn injury and appeared to correlate to monocyte-macrophage aclivalion [19]. Inlerestingly, aniibodies directed against CDl 4 were able to induce IL-1 and IL-6 production by monocyles [20], Therefore, the analysis of sCD14 may represent a useful tool lo study lhe influence of anti-CD4 ireaiment on monocytes.…”

Section: Introductionmentioning

confidence: 99%

Reduction of monocyte-macrophage activation markers upon anti-CD4 treatment. Decreased levels of IL-1, IL-6, neopterin and soluble CD14 in patients with rheumatoid arthritis

Horneff

Sack

Kalden

et al. 1993

Clinical and Experimental Immunology

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SUMMARYAnti-CD4 MoAbs have been successfully used in initial treatment trials of rheumatoid arthritis. Otie remarkable feature of this therapy was the early reduction of synovitis along with a decrease ofthe erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP). Since not only T helper celis. but also monocytes-maerophages bear the CD4 antigen, the question was raised whether the immediate elTects observed may have been in part due to an influence on the mononuclear phagocyte system. Inimediately after MoAb infusions, a significant reduction ofthe absolute peripheral blood monocyte countdown to 30"^ (/'<0-001) was noted within the firsl hour of injection. In contrast to strikingly elevated levels of soluble CD4 after treatment which was indicative ofT cell lysis, soluble CD14 levels did not rise, but rather decreased from previously elevated levels. Before treatment, aetivation ofthe monocyte-macrophage system had been signified by elevated serum levels of IL-I, IL-6. CRP and neopterin as well as a marked in vitro production of IL-I. tumour necrosis faetoralpha (TNF-cr) and IL-6. Subsequent anti-CD4 treatment resulted in a rapid and significant reduction of monocyte-derived circulating cytokines and mediators concordant with a reduced capacity to produce IL-I. TTJF-a, and IL-6 in those paiients who demonstrated clinical benefits. Therefore, studies of monocyte aetivation markers may be useful in identifying subsequent responders to anti-CD4 therapy.

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Human monocyte activation induced by an anti-CD14 monoclonal antibody

Cited by 56 publications

References 16 publications

CD14 is involved in control of human immunodeficiency virus type 1 expression in latently infected cells by lipopolysaccharide.

CD14 is involved in control of human immunodeficiency virus type 1 expression in latently infected cells by lipopolysaccharide.

Increased Circulating Soluble Cd14 Is Associated With High Mortality In Gram-Negative Septic Shock

Reduction of monocyte-macrophage activation markers upon anti-CD4 treatment. Decreased levels of IL-1, IL-6, neopterin and soluble CD14 in patients with rheumatoid arthritis

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